A Clinical Trial to study the safety and efficacy of HDLD-092320 Tablet in patients with Drug Induced Liver Injury (an injury of the liver that may occur when you take certain medicines).
Scientific Title of Study
A Prospective, Randomized, Double-Blind, Placebo-controlled, Multicentric, Comparative, Two-arm followed by an Open-Label, Single arm Clinical Study to Evaluate the Safety and Efficacy of HDLD-092320 in Participants with Drug Induced Liver Injury (DILI)
Trial Acronym
DILI
Secondary IDs if Any
Secondary ID
Identifier
HWC/MSCD/PP/055/2024, Version-1.1, Dated: 07 Jan 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Manish Kumar Singh
Designation
Consultant Physician
Affiliation
Maya Hospital and Maternity Centre
Address
343-E Block, Ground Floor, Department of General Medicine, Panki, Kanpur-208020, Uttar Pradesh, India
Kanpur Nagar UTTAR PRADESH 208020 India
Phone
7376070024
Fax
Email
drmanishkumar820@gmail.com
Details of Contact Person Scientific Query
Name
Dr Rajesh Kumawat
Designation
Head - Medical services and Clinical development
Affiliation
Himalaya Wellness Company
Address
Room no 302 3rd floor Medical services and clinical development
department Himalaya Wellness Company Makali
Bangalore
KARNATAKA
562162
India
Bangalore Rural KARNATAKA 562162 India
Phone
8067549904
Fax
Email
rajesh.kumawat@himalayawellness.com
Details of Contact Person Public Query
Name
Dr Soorya Nayaran H
Designation
Manager - Clinical Operations
Affiliation
Himalaya Wellness Company
Address
3rd floor Medical services and clinical development department
Himalaya Wellness Company Makali
Bangalore
KARNATAKA
562162
India
Bangalore Rural KARNATAKA 562162 India
Phone
8067549919
Fax
Email
dr.sooryanarayan.h@himalayawellness.com
Source of Monetary or Material Support
Himalaya Wellness Company Makali Bangalore Karnataka 562162
Primary Sponsor
Name
Himalaya Wellness Company
Address
Makali Bangalore 562162 India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Nil
Nil
Countries of Recruitment
India
Sites of Study
No of Sites = 7
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Tinu Garg
ESIC Medical College and Hospital
Room No. 2012, Second Floor, Department of Respiratory Medicine, OPD Building, ESIC Medical College and Hospital, NH-3, NIT, Faridabad-121001, Haryana, India. Faridabad HARYANA
9891011328
tinugarg87@gmail.com
Dr Piyush Arora
Jawahar lal Nehru Medical College
Jawahar lal Nehru Medical College,
Kala Bagh, Ajmer, Rajasthan-305001, India Ajmer RAJASTHAN
98870 88122
doctor.piyusharora@gmail.com
Dr Mohammad Shameem
JN Medical College and Hospital
JN Medical College and Hospital,
Department of Tuberculosis and Chest Disease Aligarh Muslim University, Aligarh UP- 202002 India. Aligarh UTTAR PRADESH
(1) Medicine Name: HDLD-092320, Reference: NA, Route: Oral, Dosage Form: Gutika/Vati/Ghana Vati/Tablets, Dose: 640(mg), Frequency: bd, Bhaishajya Kal: Adhobhakta, Duration: 70 Days, anupAna/sahapAna: No, Additional Information: Investigational Product Two tablets twice daily orally after food for 70 days
2
Comparator Arm
Drug
Other than Classical
(1) Medicine Name: Placebo, Reference: NA, Route: Oral, Dosage Form: Gutika/Vati/Ghana Vati/Tablets, Dose: 640(mg), Frequency: bd, Bhaishajya Kal: Adhobhakta, Duration: 14 Days, anupAna/sahapAna: No, Additional Information: Placebo Two tablets twice daily orally after food for 14 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.Adult male and female participants aged between 18 and 65 years.
2. Participants diagnosed with DILI as defined by any one of the following: (a) serum AST or ALT More than 5 times upper limit of normal (ULN) or ALP More than 2 times ULN (or pretreatment baseline if baseline is abnormal) on two separate occasions at
least 24 h apart (b) total serum bilirubin More than 2.5 mg/dl along with elevated serum AST, ALT, or ALP level or (c) INR More than 1.5 with elevated serum AST, ALT, or ALP.
3.Participants with mild (1+) to moderate (2+) cases of DILI as per Drug-Induced Liver Injury Network(DILIN).
4. Roussel Uclaf Causality Assessment Method (RUCAM) score more than or equal to 3 points.
5. Participants whose treatment regimen (Antitubercular, Antiretroviral, Anticonvulsant and Analgesics) are expected to use at least 3 months from the date of enrollment.
6.Participants who have not participated in any other similar clinical study within the last 3 months of screening.
7. Women of child-bearing potential and men with partners of child-bearing
potential must agree to use adequate contraception (hormonal or barrier
method of birth control) prior to study entry, for the duration of study
participation, and for 90 days following completion of therapy.
Note: A woman of child-bearing potential is any female (regardless of sexual
orientation, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:
a. Has not undergone a hysterectomy or bilateral oophorectomy; or
b. Has not attained menopause (Women not menstruating for at least 12
consecutive months).
8.Male participants who are willing to refrain from donating sperm from first admission to the study until 90 days after the study completion.
9.Participants willingly sign informed consent and follow the study procedure.
ExclusionCriteria
Details
1.Participants with acute viral, autoimmune, alcoholic and non-alcoholic fatty liver disease, or other types of hepatitis.
2. Acute liver failure or liver function decompensation, such as hepatic encephalopathy, ascites for duration less than 26 weeks.
3.Known case of Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus(HCV), Hepatitis E Virus HEV).
4.History of Cirrhosis or its complications (like HCC, Portal HTN, Liver failure).
Complications may involve:
a. Participants listed for living-related or orthotopic liver transplantation
b. Participants with a history of hepatocellular carcinoma (HCC) or history of HCC treatment.
c. Evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly.
d. Other organ failure due to DILI.
5. Other causes of Steatosis (Wilson Disease, Medications, Severe malnutrition).
6. Other laboratory parameters
a. Anemia (Hb less than 8gm/dl) or thrombocytopenia (platelet count below 50,000 platelets per microliter)
b. Serum creatinine is more than 1.5 times ULN
7.Participants with uncontrolled clinically significant serious conditions like severe anemia, severe cardiovascular disease, respiratory, hepatic, neurological, psychiatric, or malignancy/bleeding disorder or other major systemic disease or
participants with short life expectancy that, according to the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
8.Participants with severe DILI (grade 3+, 4+, 5+) as diagnosed with DILI-N
9.Any other conditions (physical, psychological, or social) that can interfere with the participant’s compliance to the study in the opinion of the Investigator.
10.Pregnant, as assessed by UPT & history of amenorrhea or lactating women.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Treatment Phase:
1. Reduction in Serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment.
2.Percentage of participants with normalization of serum ALT, AST, ALP, TBil, on day 7(±3 days) and serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment.
Adjuvant Phase:
1. Percentage of participants with normalization/non-significant LFT parameters(Serum ALT, AST, ALP, TBil, INR) throughout the adjuvant phase (at various visits).
2. Proportion of participants with recurrence of DILI as per LFT assessment (Serum ALT, AST, ALP, TBil, INR) during adjuvant phase.
Treatment Phase:
Treatment Visits (T-V)
Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit
Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization
Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment
Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit.
Adjuvant Phase:
Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit
Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment
Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit
Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment
Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit
Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
Secondary Outcome
Outcome
TimePoints
Treatment Phase-
1.Improvement in liver injury symptoms using liver injury symptom evaluation scale.
Adjuvant Phase-
1.Assessment of Gastrointestinal Symptom Rating Scale (GSRS).
2.Assessment of liver injury symptoms using liver injury symptom evaluation scale.
3.Assessment of quality of life using questionnaires.
Treatment Phase -
1.Treatment-Visit 2/ (T-V2)/ (Day 1)- Baseline/ Enrollment and Randomization
2. Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period)- End of treatment visit.
Adjuvant Phase-
1. Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period)- Follow-Up Visit
2. Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period)- Follow-Up Visit
3. Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period)- End of the study
Target Sample Size
Total Sample Size="120" Sample Size from India="120" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 2
Date of First Enrollment (India)
10/03/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The study is divided into two phases, Treatment phase and Adjuvant phase.
Treatment phase: This will be a randomized, double-blind, placebo-controlled, comparative, two-arm clinical study. Participants will be examined for eligibility criteria during the screening period (within 7 days prior to randomization). After signing the informed consent form, participants who fulfill the eligibility criteria will be enrolled into the study. A total of 120 participants will be enrolled to have at least 100 evaluable participants. Attempt would be made to enroll at least 20 participants in respective category (Antitubercular, Antiretroviral, Anticonvulsant and Analgesics) of DILI causing drugs. Eligible participants will be randomized into either of the treatment arms, i.e., Arm 1 or Arm 2 in 1:1 ratio.
Adjuvant phase: This will be an open-label single-arm study. Drug causing DILI will be reinitiated with same dose or dose titration along with HDLD-092320 for all the subjects as per the discretion of investigator based on LFT parameters/clinical conditions. Participants who are required to take alternative drugs for reinitiation in the adjuvant phase should be withdrawn from the study based on the discussion with investigator and sponsor.
Study End Points:
Efficacy Endpoint: (Treatment Phase) 1. Reduction in Serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment. 2. Percentage of participants with normalization of serum ALT, AST, ALP, TBil, on day 7(±3 days) and serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment. 3. Improvement in liver injury symptoms using liver injury symptom evaluation scale.
Efficacy Endpoint: (Adjuvant Phase) 1. Percentage of participants with normalization/non-significant LFT parameters (Serum ALT, AST, ALP, TBil, INR) throughout the adjuvant phase (at various visits).
2. Proportion of participants with recurrence of DILI as per LFT assessment (Serum ALT, AST, ALP, TBil, INR) during adjuvant phase. 3. Assessment of liver injury symptoms using liver injury symptom evaluation scale. 4. Assessment of Gastrointestinal Symptom Rating Scale (GSRS). 5. Assessment of quality of life using questionnaires.
Safety Endpoint: 1. Incidence of adverse events during the study period. 2. Proportion of participants withdrawn from trial because of adverse events (tolerability).
Study Visits: There will be a total of 10 study visits for each participant.
Treatment Visits (T-V)
Treatment-Visit 1/ (T-V1)/ (Day -7 to Day 0): Screening Visit
Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment and Randomization
Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment
Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit
Adjuvant Visits (A-V):
Drug causing DILI will be reinitiated with same dose or dose titration after T-V4/Day 14, as per the discretion of investigator based on LFT parameters/clinical conditions. Participants who are required to take alternative drugs for reinitiation in the adjuvant phase should be withdrawn from the study based on the discussion with investigator and sponsor.
The maximum gap between end of treatment phase and start of adjuvant phase should be within 14 days.
Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit
Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment
Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit
Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment
Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit
Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study.